Publisher Health

Scientists at the Institute for Integrated Cell-Material Sciences (iCeMS) and colleagues in Japan have revealed molecular mechanisms involved in eliminating unwanted cells in the body. A nuclear protein fragment released into the cytoplasm activates a plasma membrane protein to display a lipid on the cell surface, signalling other cells to get rid of it. The findings were published in the journal Molecular Cell.
“Every day, ten billion cells die and are engulfed by blood cells called phagocytes. If this didn’t happen, dead cells would burst, triggering an auto-immune reaction,” explains iCeMS biochemist Jun Suzuki, who led the study. “It is important to understand how dead cells are eliminated as part of our body’s maintenance.”
Scientists already know that dead cells display an ‘eat me’ signal on their surface that is recognized by phagocytes. During this process, lipids are flipped between the inner and outer parts of the cell membrane via a variety of proteins called scramblases. Suzuki and his team have already identified several of these lipid-scrambling proteins, but some of their activation mechanisms have been unclear.
To solve this, the team used an array of screening approaches to study the scrambling protein called Xkr4. The broad aim was to single out the genes that are active during cell death and to specifically zoom in on Xkr4 and its associated proteins to understand how they interact.
“We found that a nuclear protein fragment activates Xkr4 to display the ‘eat me’ signal to phagocytes,” says iCeMS cell biologist Masahiro Maruoka, the first author of the study.
Specifically, the scientists found that cell death signals lead to a nuclear protein, called XRCC4, getting cut by an enzyme. A fragment of XRCC4 leaves the nucleus, activating Xkr4, which forms a dimer: the linking of identical pieces into configurations. Both XRCC4 binding and dimer formation are necessary for Xkr4 to ultimately transfer lipids on the cell surface to alert phagocytes.
Xkr4 is only one of the scrambling proteins. Others are activated much faster during cell death. The team now wants to understand when and why the Xkr4 pathway is specifically activated. Since it is strongly expressed in the brain, it is likely important for brain function. “We are now studying the elimination of unwanted cells or compartments in the brain to understand this process further,” says Maruoka.
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International genomics research led by the University of Leicester has used artificial intelligence (AI) to study an aggressive form of cancer, which could improve patient outcomes.
Mesothelioma is caused by breathing asbestos particles and most commonly occurs in the linings of the lungs or abdomen. Currently, only seven per cent of people survive five years after diagnosis, with a prognosis averaging 12 to 18 months.
New research undertaken by the Leicester Mesothelioma Research Programme has now revealed, using AI analysis of DNA-sequenced mesotheliomas, that they evolve along similar or repeated paths between individuals. These paths predict the aggressiveness and possible therapy of this otherwise incurable cancer.
Professor Dean Fennell, Chair of Thoracic Medical Oncology at the University of Leicester and Director of the Leicester Mesothelioma Research Programme, said:
“It has long been appreciated that asbestos causes mesothelioma, however how this occurs remains a mystery.
“Using AI to interrogate genomic ‘big data’, this initial work shows us that mesotheliomas follow ordered paths of mutations during development, and that these so-called trajectories predict not only how long a patient may survive, but also how to better treat the cancer — something Leicester aims to lead on internationally through clinical trial initiatives.”
While use of asbestos is now outlawed — and stringent regulations in place on its removal — each year around 25 people are diagnosed with mesothelioma in Leicestershire and 190 are diagnosed in the East Midlands. Cases of mesothelioma in the UK have increased by 61% since the early 1990s.
Until very recently, chemotherapy was the only licenced choice for patients with mesothelioma. However, treatment options start to become limited once people stop responding to their treatment.
Professor Fennell in collaboration with the University of Southampton recently made a major breakthrough in treating the disease by demonstrating that use of an immunotherapy drug called nivolumab increased survival and stabilised the disease for patients. This was the first-ever trial to demonstrate improved survival in patients with relapsed mesothelioma.
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Medical privacy has become the latest casualty of vaccination efforts, as friends, co-workers and even total strangers ask intrusive questions about personal health conditions.Peter GamlenWhen Helena Jenkins, 23, recently asked to leave work early for a vaccination appointment, her boss at a Nashville retail store was incredulous.“Well how did you get that?” he asked.Ms. Jenkins was embarrassed, but answered truthfully. “Um, my weight,” she stammered, referring to the fact that, in Tennessee, a body mass index of 30 qualified her for vaccination in early March. “I had a moment of ‘ugh,’” she said later. “It made me so uncomfortable, but it didn’t click until afterward that I definitely didn’t have to answer that.”As public health officials push to get more at-risk people vaccinated, many of the newly qualified are discovering an unwelcome side effect of vaccination: Intrusive questions about their personal health.The majority of states now have expanded vaccine eligibility to include people with underlying health conditions that put them at risk for complications from Covid-19, such as high blood pressure, a compromised immune system or obesity. As a result, the demographics of the vaccine waiting lines have shifted from mostly older people and now include many seemingly healthy people in their 20s, 30s and 40s. Young vaccine recipients say their friends and co-workers are intensely curious about the appointment process, and as a result, often ignore boundaries about personal health that they never would have crossed in the past. Some of them ask directly: “What health problem allowed you to qualify?”When Amy Coody, 43, a mental health worker in Montgomery, Ala., told her friends and colleagues she had a vaccine appointment, she was shocked when it felt like people were judging her and assuming she had taken another person’s spot in line. Ms. Coody knows that she looks young and healthy, but she qualifies for two reasons — her work takes her into hospital settings, and she also has an underlying health condition that puts her at high risk.“The hostility was definitely there,” she said. “They’d be like, ‘Wait, how did you get an appointment?’ I wasn’t prepared for that kind of reaction. It took me off guard so I eventually stopped telling people I planned to get the vaccine.”Vaccine supply issues resulted in the cancellation of two of her appointments, and the shaming even made her debate rescheduling. “I would never want to step in front of somebody who needed it,” said Ms. Coody. “Then I realized, I do need it. There are a lot of patients in hospitals waiting for care. I thought, it’s about them. It’s not about me and my shame or anybody else who doesn’t understand the situation.”Getting policed about a hidden health issue isn’t new to Ms. Coody, who has a condition called dysautonomia, a disorder of the autonomic nervous system that can cause her to suddenly pass out. She said the vaccine shaming she has experienced was similar to when she’s been confronted after parking in a handicapped space, even though she has a tag that allows her to park there.“People come up to me and say, ‘You’re young and you obviously don’t have an illness so why are you taking a handicap spot?’” Ms. Coody said. “Even though it’s none of their business, I feel the need to defend myself. If more people realized there are invisible illnesses out there, maybe they might be a little more respectful about it.”Even total strangers waiting in vaccine lines have felt justified in interrogating someone who looks young and healthy. Those on the receiving end of the questions say the implication is that they must have cheated and jumped the line.Joanna Hua, 23 and a graduate student at Georgetown University, was standing in line for her second dose recently when an older woman she’d never met confronted her. “She looked at me and said, ‘You look very young to be getting the vaccine,’” Ms. Hua recounted. “She asked me, ‘How did you end up being able to qualify for one?’”Ms. Hua said she was taken aback by the question. She told the woman truthfully that she qualified because she worked in a grocery store, but she didn’t mention that she also qualified based on her weight. She said another young woman in line near her also nervously explained her reasons for qualifying.“I felt an instinctive need to justify myself,” said Ms. Hua. “It felt almost accusatory and invasive to ask about it. I think there is some sort of idea going around that people are just taking advantage and trying to get a vaccine whenever possible. I don’t doubt that some people do that. But to have a stranger come up and ask you?”Tanmoy Lala Das, a medical and doctoral student in New York City, has been helping with vaccination efforts in Manhattan, giving shots to patients and helping as a patient navigator. He said overall the experience at vaccination centers has been upbeat, and everyone is collegial and happy to be there. But he has, on occasion, heard people asking others about personal health issues while waiting in line for their shots.“I’ve overheard people ask, ‘So what brings you in today?’” Mr. Das said. “The less stigmatized conditions people are open to talking about. They’d laugh and say, “Oh, you know, diabetes.’ I think the ones who are more sensitive, they say, ‘Oh, I just got a spot.’”It doesn’t help that many people know someone who has jumped the line by claiming to be a teacher or a smoker or lying about a health condition. In New York a fitness instructor got vaccinated by claiming to be an educator, and in Florida two women even “dressed up as grannies” to get the vaccine.“I think in New York, people are trying to figure out these dynamics of are you getting the dose because it was left over, or a condition that qualifies you or did you lie about something,” said Mr. Das. “The honest reality is I know people who have cut the line and lied about things — 29-year-old people who have gotten vaccines who don’t have pre-existing conditions. But I think most people are not lying. The goal is to vaccinate everyone.”Rhonda Wolfson, who lives in Toronto, said that in places where the vaccination process still is age-restricted, it has created a different privacy problem, casting light on the fact that a person is above a certain age. Ms. Wolfson qualified for a pilot vaccination program in Ontario for people aged 60 to 64, and she realized that talking about her vaccination would reveal her as a sexagenarian to people who thought she was younger.“I have one friend in her 40s, and she knows I’m older, but she doesn’t know my exact age,” said Ms. Wolfson. “She’s never asked, and I’ve never offered. I spoke to her last week and in my excitement I mentioned, ‘OMG, I got vaccinated.’ I could almost hear her pause, ‘Oh, you’re that age.’”In some circles, the stigma of early vaccination is even more concerning because it could dissuade at-risk people from getting the shot. In the gay community, for instance, a young person who gets vaccinated in the early group might be seen to be immunocompromised.“In the gay community there is this assumption that if you are getting the vaccine right now you must be secretly H.I.V. positive,” said Mr. Das, who is gay. “It has become an assumption in the community that if you’re a gay and you post a picture of the vaccine card, you’re positive and haven’t told us. I always talk to my friends and tell them, ‘Don’t assume things.’”Mr. Das said he is hopeful that any stigma or medical privacy issues associated with early vaccination will disappear once vaccine appointments are open to everyone. President Biden has urged all states to expand medical eligibility to the general population by May 1, and many states, including Alaska, Arizona, Georgia and Mississippi, have already made the change.“The sooner we get to vaccinating everyone, I think this question of ‘Oh, what qualified you?’ will stop,” Mr. Das said. “Once that goes away hopefully these barriers will break down, and people won’t keep asking these very personal questions.”

As U.S. manufacturers hit their stride, vaccine scarcity will soon turn to plenty as much of the world goes begging. And vaccine makers need answers now about what to do with the coming surplus.WASHINGTON — Biden administration officials are anticipating the supply of coronavirus vaccine to outstrip U.S. demand by mid-May if not sooner, and are grappling with what to do with looming surpluses when vaccine scarcity turns to glut.President Biden has promised enough doses by the end of May to immunize all of the nation’s roughly 260 million adults who are eligible for shots. But between then and the end of July, the government has locked in commitments from manufacturers for enough vaccine to cover another 100 million people — or about 70 million more than the nation’s entire population.Whether to keep, modify or redirect those orders is a question with significant implications, not just for the nation’s efforts to contain the virus but also for how soon the pandemic can be brought to an end. Of the vaccine doses given globally, about three-quarters have gone to only 10 countries. At least 30 countries have not yet injected a single person.And global scarcity threatens to grow more acute as nations and regions clamp down on vaccine exports. With infections soaring, India, which had been a major vaccine distributor, is now holding back nearly all of the 2.4 million doses manufactured daily by a private company there. That action follows the European Union’s decision this week to move emergency legislation that would curb vaccine exports for the next six weeks.Biden administration officials who are inclined to hold on to the coming U.S. surplus point to unmet need and rising uncertainty: Children and adolescents are still unvaccinated, and no one is certain if or when immunity could wear off, which could require scores of millions of booster shots.“We want to, largely, be a part of the global solution here,” Jen Psaki, the White House press secretary, said this week. But she added, “There are still a number of factors that are unpredictable that we need to plan for to the best of our ability, including the variants and the impact and what will be most effective, as well as what will work best with children.”Vaccine manufacturers and some top federal officials say decisions about what to do with extra orders must be made within weeks, or the uncertainty could slow production lines. The manufacturing process can take up to 10 weeks, and changes for a foreign market need time. The regulatory rules that govern vaccine shipments present another hurdle, as does the limited storage life of the drug substances that make the vaccine.Vials in the nation’s bottling plants in Michigan and Indiana are being labeled for use at home. If their destination is unclear, either the production line must pause or vials directed for overseas may need to be relabeled.Once the doses are shipped out to states, federal regulations prohibit recalling them even if they are not needed domestically. And vials cannot sit in storage forever: While vaccine itself can last up to a year in a frozen state, once bottled it must be used within four to six months.All these variables threaten to complicate what so far has been relatively smooth sailing for the Biden administration. Thanks in part to the federal government’s determined assistance over many months, vaccine manufacturers have been steadily increasing their output, and states have snapped up new doses as fast as the government could deliver them.Where to go from here is a matter of intense debate.Clinical trials to determine which vaccines work for the nation’s adolescents and children are continuing and most likely will not neatly wind up at the same time. By the end of spring, for example, Moderna and Pfizer are hoping for interim results on how their vaccines would work for the nation’s 30-some-million adolescents. But Moderna, at least, does not expect results for children under 12 until after the school year starts next fall.The administration could hang on to doses from those two manufacturers while it awaits findings, only to discover later that another vaccine whose trials began later — say Johnson & Johnson’s — is a better option.If one or more of the three authorized vaccines turn out to provide only brief protection against Covid-19, scores of millions of more doses could be required for booster shots. But when that answer will come is also uncertain.A woman received one of New Jersey’s first Johnson & Johnson vaccine doses this month. Of all the vaccine doses given globally, about three-quarters have gone to only 10 countries.Bryan Anselm for The New York TimesFederal health officials have also discussed canceling or reducing some orders from Moderna and Pfizer in return for the promise of a fresh supply this fall of either pediatric doses or shots of a new vaccine that has been reconfigured to work against the fast-spreading variants.There is some push for that from the manufacturers, whose vaccines are coveted by other high-income countries. But it would also deprive federal officials of the power to decide which nations get the surplus doses, as well as the humanitarian and diplomatic credit it would reap from sending the vaccine to countries in greater need.For all these reasons, senior officials say, the administration is leaning toward keeping the doses it has ordered then at some point directing the excess to other nations in bilateral deals or giving it to Covax, an international nonprofit organization backed by the World Health Organization that is trying to coordinate equitable distribution of vaccine. The Biden administration has already donated $4 billion to that international effort.Mr. Biden has stressed that his top priority is to protect Americans, but pressure is growing to share the U.S. stock. The United States has ordered a billion doses from the three federally authorized manufacturers and AstraZeneca, whose vaccine is not yet cleared for emergency use in the States but has been authorized by more than 70 countries. It recently announced that it was negotiating a deal with Johnson & Johnson for enough doses to cover another 100 million.Taken together, the supply would be enough to vaccinate 650 million people — nearly twice the U.S. population. With the world’s highest death toll from Covid-19, the United States has fully vaccinated 14 percent of its population.Last week, the White House announced that it would share four million doses of AstraZeneca’s vaccine with Mexico and Canada, but emphasized that no Americans would lose out because the vaccine has not been deployed here yet.That is a trickle compared with the 300 million AstraZeneca doses the federal government has ordered, enough to cover 150 million people with the two-dose regimen. Senior administration officials say tens of millions of those doses can be released now or imminently, and tens of millions of unbottled doses possibly could also be given away.Brazil is particularly eager for help. With more than 300,000 lives lost, the country has the second-highest death toll and has fully vaccinated less than 2 percent of its population.“After we do take care of the really difficult situation we’ve had in our own country with over 535,000 deaths, we will obviously, in the future, have surplus vaccine, and there certainly is a consideration for making that vaccine available to countries that need it,” Dr. Anthony S. Fauci, the government’s top infectious disease expert, said at a White House news conference on Wednesday.He has cast early May, when the Biden administration wants states to open up vaccinations to all adults, as a turning point. In an interview this week, he said it was likely that anyone who wants a vaccine would be able get one then.Some will not want to be vaccinated, although their numbers appear to be dwindling. According to a Pew Research Center poll this month, 69 percent of the public intends to get inoculated or already has.In the summer, the U.S. production outlook brightens further. Pfizer and Moderna together have promised enough doses to cover another 100 million people by the end of July.Pfizer continues to beef up its production lines. And Moderna is hoping to win regulatory approval to increase the number of doses in each vial by at least 40 percent, although shortages of specialized syringes might hinder that plan.A shipment of the AstraZeneca vaccine arriving in Ethiopia this month, as part of the United Nations-led Covax program.Amanuel Sileshi/Agence France-Presse — Getty ImagesJohnson & Johnson has been slower to scale up its manufacturing in the United States and is now racing to deliver as many as 24 million doses manufactured at its Dutch plant by the end of the month, according to federal officials. The Food and Drug Administration just certified its new bottling operation in Indiana and is expected any day to approve its vaccine production lines at a Baltimore plant.But while Johnson & Johnson has lagged behind the other manufacturers, its technology carries enormous promise for mass production because it can deliver many more doses per lot.Later this year, when Merck & Company is expected to begin producing Johnson & Johnson’s vaccine, it could churn out 100 million doses a month — or as much as Pfizer and Moderna together deliver monthly. The White House hailed the deal between Johnson & Johnson and Merck, but by the time production gets up to speed, those doses may be bound for a growing surplus or for export.One option is to ship the frozen vaccine that will be manufactured in Merck’s plant overseas, where it can be bottled much more cheaply. Of the $10 that the federal government has agreed to pay for a dose of Johnson & Johnson’s vaccine, the drug substance itself accounts for only about 30 cents, federal officials said. The rest is the so-called fill-and-finish cost.If AstraZeneca wins emergency use authorization from U.S. regulators, that will throw still more shots into the mix. Officials expect about 50 million doses to be ready for delivery in May.But Biden administration officials are skittish about AstraZeneca’s vaccine. It appears to be roughly as effective as Johnson & Johnson’s but requires an additional shot, meaning a more complicated rollout. Some health officials worry that if there are already enough doses in the pipeline to cover every adult who wants a shot, introducing a fourth vaccine will just confuse people.On the other hand, if the administration decides to donate the AstraZeneca doses without offering any to its own citizens, other countries might conclude that the United States lacks confidence in the vaccine’s safety or effectiveness.“As we gain more confidence in the doses that we have and the ability or the need or not to be boosting, then we can make a more definitive statement about what the role of the AZ product is going to be in the United States” should it gain clearance, Dr. Fauci said in an interview this week, “but right now I think it’s too premature to say anything.”Sheryl Gay Stolberg

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While Europe faces a shortage of vaccines and governments argue about who gets what, one company in north Wales is producing jabs solely for the UK population.Almost all of the UK’s AstraZeneca supply comes through here; it’s where the vaccine’s filled into sterile vials, inspected dozens of times, and sent out for distribution.The Prime Minister Boris Johnson called it a “saviour of humanity” and it’s fair to say the staff inside are feeling immense pressure – and pride – from their role in the vaccination programme.BBC Breakfast was given world-first access to the production line.Camera/Edit: Brijesh PatelProducer: Josh ParryReporter: Jayne McCubbin

Scientists can now sequence an entire genome overnight. This technology has been the key tool in identifying and tracking Covid […]

Scientists have identified new genetic clues in people who’ve had small and often apparently ‘silent’ strokes that are difficult to treat and a major cause of vascular dementia, according to research funded by the British Heart Foundation (BHF) and published in The Lancet Neurology.
Researchers discovered changes to 12 genetic regions in the DNA of people who have had a lacunar stroke — a type of stroke caused by weakening of the small blood vessels deep within the brain. Over time, damage to the blood vessels and subsequent interruption to blood flow can lead to long-term disability, causing difficulty with thinking, memory, walking and ultimately dementia.
There are few proven drugs to prevent or treat lacunar strokes. The blood vessels affected are less than a millimetre wide and a lacunar stroke can strike without the person knowing. It’s not usually until someone has had a number of these strokes and starts to see signs of dementia that they realise something is wrong.
To date, only one genetic fault has been associated with lacunar strokes. However, after over a decade of research, Professor Hugh Markus and his team at the University of Cambridge working with researchers from around the world now believe their genetic breakthrough holds the key to finding much-needed treatments for lacunar stroke and vascular dementia.
Researchers scanned and compared the genetic code of 7,338 patients who had a lacunar stroke with 254,798 people who had not. Participants were recruited from across Europe, United States, South America and Australia after they attended hospital and had an MRI or CT brain scan.
They discovered that many of the 12 genetic regions linked to lacunar strokes were involved in maintaining the neurovascular unit — the part of the brain that separates the blood vessels from the brain and ensures that nerves function normally. These genetic changes are thought to make the small blood vessels ‘leakier’, causing toxic substances to enter the brain, and meaning that messages travelling around the brain slow down or don’t arrive at all.

Heightened activity in the brain, caused by stressful events, is linked to the risk of developing a rare and sometimes fatal heart condition, according to research published today (Friday) in the European Heart Journal.
The study found the greater the activity in nerve cells in the amygdala region of the brain, the sooner the condition known as Takotsubo syndrome (TTS) can develop. The researchers suggest that interventions to lower this stress-related brain activity could help to reduce the risk of developing TTS; these could include drug treatments or techniques for lowering stress.
TTS, also known as “broken heart” syndrome, is characterised by a sudden temporary weakening of the heart muscles that causes the left ventricle of the heart to balloon out at the bottom while the neck remains narrow, creating a shape resembling a Japanese octopus trap, from which it gets its name. Since this relatively rare condition was first described in 1990, evidence has suggested that it is typically triggered by episodes of severe emotional distress, such as grief, anger or fear, or reactions to happy or joyful events. Patients develop chest pains and breathlessness, and it can lead to heart attacks and death. TTS is more common in women with only 10% of cases occurring in men.*
The amygdala is the part of the brain that controls emotions, motivation, learning and memory. It is also involved in the control of the autonomic nervous system and regulating heart function.
“The study suggests that the increased stress-associated neurobiological activity in the amygdala, which is present years before TTS occurs, may play an important role in its development and may predict the timing of the syndrome. It may prime an individual for a heightened acute stress response that culminates in TTS,” said Dr Ahmed Tawakol, co-director of the Cardiovascular Imaging Research Center at Massachusetts General Hospital and Harvard Medical School (Boston, USA), who led the study.
“We also identified a significant relationship between stress-associated brain activity and bone marrow activity in these individuals. Together, the findings provide insights into a potential mechanism that may contribute to the ‘heart-brain connection’.”
In the first study to look at brain scans using F-fluorodeoxyglucose positron emission tomography/computed tomography (PET-CT) to assess brain activity before TTS develops, Dr Tawakol and colleagues analysed data on 104 people with an average age of 68 years, 72% of whom were women.

He was a top executive at Memorial Sloan Kettering before resigning over payments from health care companies. He went on to lead cancer research at AstraZeneca.Dr. José Baselga, a renowned cancer researcher and pharmaceutical executive whose work helped transform the treatment of breast cancer patients, died on Sunday. He was 61.His employer, the drug maker AstraZeneca, confirmed the death but did not say where he died. The Washington Post reported that he died at his home in the Cerdanya region of Spain and that he had maintained another home in New York City. His family confirmed that the cause was Creutzfeldt-Jakob disease, a rare neurological disorder, but declined to comment further.Dr. Baselga had worked at AstraZeneca since 2019 as the executive vice president for research and development in oncology. Before that he was chief medical officer at Memorial Sloan Kettering Cancer Center in Manhattan, until he resigned in 2018 following revelations reported jointly by The New York Times and ProPublica that in his published research he had failed to disclose payments from health care companies.“His visionary leadership, deep scientific expertise and strategic insight have delivered so many achievements that we can all be proud of and that will benefit patients’ lives in the years to come,” Pascal Soriot, AstraZeneca’s chief executive, said in a statement.In a decades-long career in the United States and his native Spain, Dr. Baselga was known for his work in developing and testing targeted cancer treatments, including the breast cancer treatment Herceptin, a monoclonal antibody that zeroes in on a particular protein, known as HER2, which is implicated in aggressive and deadly breast cancers.Targeted cancer drugs allow doctors to tailor treatment to specific types of cancer cells. This can lead to fewer side effects and better results than those obtained through blunter instruments like chemotherapy.Dr. Baselga led an early-stage clinical trial of Herceptin, and his research contributed to the recognition that when the drug was combined with chemotherapy, it extended the lives of women with so-called HER2-positive breast cancer, said Dr. Clifford Hudis, the chief executive of the American Society of Clinical Oncology.“It’s the dream that everybody has when you do research,” said Dr. Hudis, who had known Dr. Baselga since the 1980s. “He was dedicated to translational research, and he was unbelievably demanding when it came to execution. He expected everything and everybody to understand his vision and to deliver on it.”Dr. Baselga was also involved in the clinical development of other breast cancer drugs like Perjeta, or pertuzumab, and Afinitor, or everolimus. More recently he studied the development of drugs targeting tumors that have a mutation known as PI3K. His work also focused on drug resistance in some cancers.José Baselga was born in Barcelona on July 3, 1959, and earned his medical and doctoral degrees from the Autonomous University of Barcelona. He caught the attention of cancer researchers after participating in a medical fellowship at Memorial Sloan Kettering, where he worked with Dr. John Mendelsohn in researching the use of monoclonal antibodies in targeting certain proteins associated with aggressive cancers, including lung and breast cancers.Dr. Larry Norton, a senior vice president at Memorial Sloan Kettering and the medical director of the hospital’s Evelyn H. Lauder Breast Center, quickly took an interest in Dr. Baselga and served as an early mentor. “He was an artist,” Dr. Norton recalled, adding that he had “a driving force within him, and he would focus all of his energies on accomplishing what was necessary to fulfill that vision.”Dr. Baselga returned to Spain in 1996 to found the Vall d’Hebron Institute of Oncology at Vall d’Hebron University Hospital in Barcelona. Under his leadership, the center became an international powerhouse in cancer research, testing targeted cancer therapies in early-stage clinical trials. Dr. Baselga became a well-known figure in Spain.“Spain was not known in the world as a cancer research place,” Dr. Antoni Ribas, the president of the American Association for Cancer Research, who did his medical residency at Vall d’Hebron just before Dr. Baselga assumed his role there, said in a phone interview. “He put Vall d’Hebron, Barcelona and Spain on the map of cancer research.”Following a stint from 2010 to 2013 at Massachusetts General Hospital, where he was the chief of the division of hematology and oncology, Dr. Baselga returned to Memorial Sloan Kettering in 2013 to become physician in chief and, later, chief medical officer.He also held several leadership roles in the world of cancer research, including president of the American Association for Cancer Research and editor of Cancer Discovery and other medical journals.Dr. Baselga resigned from Sloan Kettering in September 2018 under pressure after The Times and ProPublica, the nonprofit investigative journalism outfit, reported that he had failed to disclose millions of dollars in payments from drug and health care companies in dozens of research articles in The New England Journal of Medicine and other publications.In resigning, he said he was “extremely proud” of his work at Sloan Kettering and added, “It is my hope that this situation will inspire a doubling down on transparency in our field.”His departure led the cancer center to overhaul its conflict-of-interest policy. Dr. Baselga later stepped down from the boards of Bristol-Myers Squibb and the radiation equipment manufacturer Varian Medical Systems.The Post said his survivors include his wife of 30 years, Silvia Garriga; four children, Marc Baselga, Clara Baselga-Garriga, Pepe Baselga-Garriga and Alex Baselga-Garriga; his mother, Esther Torres; two sisters; and a brother.AstraZeneca announced in January 2019 that it had hired Dr. Baselga to lead its cancer research. In his time with the company, Mr. Soriot, AstraZeneca’s chief executive, said, Dr. Baselga had championed the company’s collaboration with Daiichi Sankyo to develop two cancer treatments and built a “world-class” team of cancer researchers at the company.“I will continue to be inspired by his work and vision,” Mr. Soriot said.